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The ascochlorin derivative, AS-6, inhibits TNF-α-induced adhesion molecule and chemokine expression in rat vascular smooth muscle cells

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Author(s)
Keun-Gyu ParkKyeong-Min LeeYoung-Chae ChangJunji MagaeKunio AndoKwon-Bae KimYoon-Nyun KimHye-Soon KimJoong-Yeol ParkKi-Up LeeIn-Kyu Lee
Keimyung Author(s)
Park, Keun GyuKim, Kwon BaeKim, Yoon NyunKim, Hye Soon
Department
Dept. of Internal Medicine (내과학)
Institute for Medical Science (의과학연구소)
Journal Title
Life Science
Issued Date
2006
Volume
80
Issue
2
Keyword
Ascochlorin-6AtherosclerosisCX3CL1MCP-1PPARγVascular smooth muscle cellVCAM-1
Abstract
Vascular inflammation induced by the proinflammatory cytokine/NF-κB pathway is one of the key mechanisms in the development of atherosclerosis. Peroxisome proliferators-activated receptor-γ (PPARγ) plays an important role in the prevention of arterial inflammation and formation of atherogenesis. Herein we examine the effects of a newly identified synthetic PPARγ ligand, ascochlorin-6 (AS-6), on TNF-α-stimulated NF-κB activity and inflammatory molecule expression in vascular smooth muscle cells (VSMCs). AS-6 successfully inhibited TNF-α-stimulated NF-κB activity and inflammatory molecule expression, including vascular cell adhesion molecule-1 (VCAM-1), monocyte chemotactic protein-1 (MCP-1), and fractalkine (CX3CL1). Transient transfection with an [NF-κB]×4 luciferase reporter construct showed that AS-6 inhibition of TNF-α-stimulated NF-κB activation was PPARγ-dependent. The effects of AS-6 on TNF-α-stimulated VCAM-1 and CX3CL1 expression were abolished in cells transfected with an adenovirus expressing dominant-negative PPARγ and in cells treated with a PPARγ specific inhibitor, GW9662, confirming again that the anti-inflammatory effect of AS-6 was PPARγ-dependent. The inhibitory effects of AS-6 on TNF-α-stimulated inflammatory gene expression and NF-κB activation were more potent than those of rosiglitazone and pioglitazone. This study shows that AS-6 reduces the inflammatory response to TNF-α in VSMCs. The data suggest the possibility that AS-6 can be used to prevent the development and progression of atherosclerosis.
Keimyung Author(s)(Kor)
박근규
김권배
김윤년
김혜순
Publisher
School of Medicine
Citation
Keun-Gyu Park et al. (2006). The ascochlorin derivative, AS-6, inhibits TNF-α-induced adhesion molecule and chemokine expression in rat vascular smooth muscle cells. Life Science, 80(2), 120–126. doi: 10.1016/j.lfs.2006.08.030
Type
Article
ISSN
0024-3205
Source
https://www.sciencedirect.com/science/article/pii/S0024320506006606?via%3Dihub
DOI
10.1016/j.lfs.2006.08.030
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/36301
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
3. Research Institutues (연구소) > Institute for Medical Science (의과학연구소)
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